By Erica Check Hayden of Nature magazine
Scientists have identified the molecular players central to an incurable brain injury common in premature babies, and have shown how such injuries might one day be treated, sparing people from lifelong conditions such as cerebral palsy.
In babies born before their lungs are fully developed, lack of oxygen can disrupt nerve cells' ability to make a protective coating, called myelin, that makes up the brain's 'white matter'. Without myelin, brain cells die, leaving children vulnerable to neurological deficits such as cerebral palsy.
Some 20% of babies born before 6.5 months gestation experience lasting brain damage (see 'The most vulnerable brains').
"We have become very good at keeping these premature babies alive, but we have no strategy to prevent the long-term neurological consequences that can occur in them," says Vittorio Gallo, a neuroscientist at the Children's National Medical Center in Washington DC.
Writing in Nature Neuroscience, David Rowitch at the University of California, San Francisco, and his colleagues point the way AXIN2 was expressed in infants with white-matter brain injuries.
They also found AXIN2 in the damaged nerve cells of adults with multiple sclerosis, a disease in which the immune system attacks myelin. The AXIN2 protein interacts with proteins in the Wnt signalling pathway, which is involved in controlling many cellular processes, including development.
The authors went on to study young mice with white-matter nerve damage similar to that seen in premature babies. When the researchers injected myelin-deficient regions in the mice with a drug that prevents destruction of the AXIN2 protein, the mice grew myelin sheaths faster than untreated mice, repairing the damage.
"There's a lot of work needed before we want to seriously propose that this is going to be a therapeutic avenue," says Rowitch. "But this is the first evidence that this pathway can be manipulated therapeutically.
The study is an important demonstration that a drug might be used to repair brain damage, Gallo says. "One of the strengths of this paper is that it shows that a small molecule that affects the Wnt pathway promotes regeneration, so this shows one pharmaceutical way to treat this type of injury."
However, Stephen Back, a neurologist at the Oregon Health and Science University in Portland, points out that there is not yet proof that myelin-producing cells are stuck in arrested development in infants with brain injuries, although this has been shown both in mice and in adults with multiple sclerosis. So it is not entirely clear that a drug to speed their development would remedy such injuries.
"This work is certainly relevant to multiple sclerosis, but I would strike a cautionary note that it remains to be seen whether these myelin-producing cells are also arrested in newborn brain injury," Back says.
First author Stephen Fancy, a postdoc working with Rowitch, says that the work could be very important for multiple sclerosis. Although treatments are available for the disease, they do not repair the damage to nerve cells.
"This is going to be important in the future, both for multiple sclerosis and different types of newborn white-matter injury," Fancy says.
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This article is reproduced with permission from the magazine Nature. The article was first published on June 26, 2011.